PDS0101 Plus Pembrolizumab Under Further Evaluation in HPV16+ HNSCC

The FDA has agreed on key elements of the clinical program to support the biologic license application for the combination of PDS0101 and pembrolizumab (Keytruda) for the treatment of unresectable, recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC).¹

The regulatory input follows a successful end-of-phase 2 meeting between the FDA and PDS Biotech.

“We are very pleased with the guidance received from FDA on key elements of the clinical program that will support the submission of a Biologics License Application (BLA) for our lead asset PDS0101,” Frank Bedu-Addo, PhD, chief executive officer of PDS Biotech, stated in a press release. “The interim safety and efficacy data we presented to the FDA has allowed us to move into a registrational trial ahead of our projected schedule. This, along with the recent capital raise, allows us to efficiently advance our clinical programs.”

In June 2022, the FDA granted fast track designation to PDS0101 for use in combination with pembrolizumab in patients with recurrent or metastatic HPV16-positive head and neck cancer.²

The combination is under investigation in the phase 2 VERSATILE-002 trial (NCT04260126). Data from a prespecified interim analysis of the study presented at the 2022 ASCO Annual Meeting showed that among 17 checkpoint inhibitor–naïve patients with HPV16-positive recurrent or metastatic HNSCC who had a combined positive score (CPS) of at least 1 and for whom imaging data were available, the overall response rate was 41.2%, comprised of 2 complete responses (11.8%) and 5 partial responses (29.4%).³ Additionally, 6 patients (35.3%) achieved stable disease, and 4 patients (23.5%) had disease progression.

VERSATILE-002 enrolled patients with recurrent or metastatic HPV16-related HNSCC who were at least 18 years of age and who were either naïve or refractory to checkpoint inhibitors and who had a PD-L1 CPS of 1 or higher.⁴ Other key inclusion criteria included acceptable organ function, an ECOG performance status of 0 or 1, and recovery from any toxicity or complications if they had previously undergone major surgery or radiation of higher than 30 Gy.

Patients received 200 mg of intravenous pembrolizumab every 3 weeks plus subcutaneous injections of PDS0101 for cycles 1 through 4 and 12. Pembrolizumab was continued until progressive disease, intolerance, or up to 35 cycles.

The primary end point of the trial was best overall response of confirmed complete response or confirmed partial response. Secondary end points consisted of progression-free survival (PFS), overall survival (OS), duration of response, immune responses, and safety.

Additional data presented at ASCO showed that neither the median PFS or OS had been reached at the time of analysis. The 9-month PFS and OS rates were 55.2% (95% CI, 31.9%-78.4%) and 87.2% (95% CI, 70.4%–not evaluable), respectively.

Among 19 patients evaluable for safety, no patients required dose reduction or discontinuation with either immunotherapy agent. The median number of PDS0101 doses received was 4.0 (range, 1.0-5.0), and the median treatment duration was 2.2 months (range, 0.0-7.7). The median number of pembrolizumab doses received was 9.0 (range, 1.0-18.0), and the median duration of treatment was 5.9 months (range, 0.0-11.9).

Additionally, 94.7% of patients experienced treatment-emergent adverse effects (TEAEs). TEAEs included grade 1 in 15.8% of patients, grade 2 in 42.1%, grade 3 in 26.3%, and grade 5 in 10.5%. No grade 3 or higher TEAEs attributed to study treatment were observed per investigator assessment, and no serious treatment-related TEAEs occurred.

References

1. PDS Biotech announces successful end-of-phase 2 meeting with the FDA and preparation for the registrational trial of PDS0101 in combination with Keytruda®. News release. PDS Biotech. October 3, 2022. Accessed October 4, 2022. https://yhoo.it/3yeo8WF
2. PDS Biotechnology granted FDA fast track designation for lead candidate PDS0101. News release. PDS Biotechnology Corporation. June 2, 2022. Accessed October 4, 2022. https://bit.ly/3mSq2WL
3. Weiss J, Chintakuntlawar A, Price KA, et al. PDS0101 a novel type I interferon and CD8 T cell activating immunotherapy in combination with pembrolizumab in subjects with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2022;40(suppl 16):6041. doi:10.1200/JCO.2022.40.16_suppl.6041
4. Study of PDS0101 and pembrolizumab combination I/O in subjects with HPV16+ recurrent and/or metastatic HNSCC (VERSATILE002). ClinicalTrials.gov. Updated September 28, 2022. Accessed October 4, 2022. https://clinicaltrials.gov/ct2/show/NCT04260126